Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas.

BACKGROUND: Despite advances in detection and treatments, biliary tract cancers continue to have poor survival outcomes. Currently, there is limited data investigating the significance of socioeconomic status, race/ethnicity, and environmental factors in biliary tract cancer survival. AIM: To investigate how socioeconomic status and race/ethnicity are associated with survival. METHODS: Data from the Surveillance, Epidemiology, and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016. Socioeconomic data included smoking, poverty level, education, adjusted household income, and percentage of foreign-born persons and urban population. Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis. RESULTS: Our study included 15883 gallbladder, 11466 intrahepatic biliary, 12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases. When analyzing county-specific demographics, patients from counties with higher incomes were associated with higher survival rates [hazard ratio (HR) = 0.97, P <0.05]. Similarly, counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates (HR = 0.96, P = 0.002 and HR = 0.97, P = 0.004, respectively). CONCLUSION: Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

Patient Partnership Tools to Support Medication Safety in Community-Dwelling Older Adults: Protocol for a Nonrandomized Stepped Wedge Clinical Trial.

BACKGROUND: Preventable harms from medications are significant threats to patient safety in community settings, especially among ambulatory older adults on multiple prescription medications. Patients may partner with primary care professionals by taking on active roles in decisions, learning the basics of medication self-management, and working with community resources. OBJECTIVE: This study aims to assess the impact of a set of patient partnership tools that redesign primary care encounters to encourage and empower patients to make more effective use of those encounters to improve medication safety. METHODS: The study is a nonrandomized, cross-sectional stepped wedge cluster-controlled trial with 1 private family medicine clinic and 2 public safety-net primary care clinics each composing their own cluster. There are 2 intervention sequences with 1 cluster per sequence and 1 control sequence with 1 cluster. Cross-sectional surveys will be taken immediately at the conclusion of visits to the clinics during 6 time periods of 6 weeks each, with a transition period of no data collection during intervention implementation. The number of visits to be surveyed will vary by period and cluster. We plan to recruit patients and professionals for surveys during 405 visits. In the experimental periods, visits will be conducted with two partnership tools and associated clinic process changes: (1) a 1-page visit preparation guide given to relevant patients by clinic staff before seeing the provider, with the intention to improve communication and shared decision-making, and (2) a library of short educational videos that clinic staff encourage patients to watch on medication safety. In the control periods, visits will be conducted with usual care. The primary outcome will be patients' self-efficacy in medication use. The secondary outcomes are medication-related issues such as duplicate therapies identified by primary care providers and assessment of collaborative work during visits. RESULTS: The study was funded in September 2019. Data collection started in April 2023 and ended in December 2023. Data was collected for 405 primary care encounters during that period. As of February 15, 2024, initial descriptive statistics were calculated. Full data analysis is expected to be completed and published in the summer of 2024. CONCLUSIONS: This study will assess the impact of patient partnership tools and associated process changes in primary care on medication use self-efficacy and medication-related issues. The study is powered to identify types of patients who may benefit most from patient engagement tools in primary care visits. TRIAL REGISTRATION: ClinicalTrials.gov NCT05880368; https://clinicaltrials.gov/study/NCT05880368. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57878.

A Predictive Decision Analytics Approach for Primary Care Operations Management: A Case Study of Double-Booking Strategy Design and Evaluation.

Primary care plays a vital role for individuals and families in accessing care, keeping well, and improving quality of life. However, the complexities and uncertainties in the primary care delivery system (e.g., patient no-shows/walk-ins, staffing shortage, COVID-19 pandemic) have brought significant challenges in its operations management, which can potentially lead to poor patient outcomes and negative primary care operations (e.g., loss of productivity, inefficiency). This paper presents a decision analytics approach developed based on predictive analytics and hybrid simulation to better facilitate management of the underlying complexities and uncertainties in primary care operations. A case study was conducted in a local family medicine clinic to demonstrate the use of this approach for patient no-show management. In this case study, a patient no-show prediction model was used in conjunction with an integrated agent-based and discrete-event simulation model to design and evaluate double-booking strategies. Using the predicted patient no-show information, a prediction-based double-booking strategy was created and compared against two other strategies, namely random and designated time. Scenario-based experiments were then conducted to examine the impacts of different double-booking strategies on clinic's operational outcomes, focusing on the trade-offs between the clinic productivity (measured by daily patient throughput) and efficiency (measured by visit cycle and patient wait time for doctor). The results showed that the best productivity-efficiency balance was derived under the prediction-based double-booking strategy. The proposed hybrid decision analytics approach has the potential to better support decision-making in primary care operations management and improve the system's performance. Further, it can be generalized in the context of various healthcare settings for broader applications.

Assessing Interventions on Crowdsourcing Platforms to Nudge Patients for Engagement Behaviors in Primary Care Settings: Randomized Controlled Trial.

BACKGROUND: Engaging patients in health behaviors is critical for better outcomes, yet many patient partnership behaviors are not widely adopted. Behavioral economics-based interventions offer potential solutions, but it is challenging to assess the time and cost needed for different options. Crowdsourcing platforms can efficiently and rapidly assess the efficacy of such interventions, but it is unclear if web-based participants respond to simulated incentives in the same way as they would to actual incentives. OBJECTIVE: The goals of this study were (1) to assess the feasibility of using crowdsourced surveys to evaluate behavioral economics interventions for patient partnerships by examining whether web-based participants responded to simulated incentives in the same way they would have responded to actual incentives, and (2) to assess the impact of 2 behavioral economics-based intervention designs, psychological rewards and loss of framing, on simulated medication reconciliation behaviors in a simulated primary care setting. METHODS: We conducted a randomized controlled trial using a between-subject design on a crowdsourcing platform (Amazon Mechanical Turk) to evaluate the effectiveness of behavioral interventions designed to improve medication adherence in primary care visits. The study included a control group that represented the participants' baseline behavior and 3 simulated interventions, namely monetary compensation, a status effect as a psychological reward, and a loss frame as a modification of the status effect. Participants' willingness to bring medicines to a primary care visit was measured on a 5-point Likert scale. A reverse-coding question was included to ensure response intentionality. RESULTS: A total of 569 study participants were recruited. There were 132 in the baseline group, 187 in the monetary compensation group, 149 in the psychological reward group, and 101 in the loss frame group. All 3 nudge interventions increased participants' willingness to bring medicines significantly when compared to the baseline scenario. The monetary compensation intervention caused an increase of 17.51% (P<.001), psychological rewards on status increased willingness by 11.85% (P<.001), and a loss frame on psychological rewards increased willingness by 24.35% (P<.001). Responses to the reverse-coding question were consistent with the willingness questions. CONCLUSIONS: In primary care, bringing medications to office visits is a frequently advocated patient partnership behavior that is nonetheless not widely adopted. Crowdsourcing platforms such as Amazon Mechanical Turk support efforts to efficiently and rapidly reach large groups of individuals to assess the efficacy of behavioral interventions. We found that crowdsourced survey-based experiments with simulated incentives can produce valid simulated behavioral responses. The use of psychological status design, particularly with a loss framing approach, can effectively enhance patient engagement in primary care. These results support the use of crowdsourcing platforms to augment and complement traditional approaches to learning about behavioral economics for patient engagement.

Appendiceal adenocarcinoma is associated with better prognosis than cecal adenocarcinoma: a population-based comparative survival study.

OBJECTIVE: Although appendiceal cancer remains a rare gastrointestinal malignancy compared with colorectal cancer, incidence rates of appendiceal cancer have increased in the last two decades. Appendiceal and cecal adenocarcinomas have distinct genomic profiles, but chemotherapy protocols for these malignancies are the same and survival outcomes between them have not been compared extensively. To this end, we conducted a comparative survival analysis of appendiceal and cecal adenocarcinomas. DESIGN: Using the Surveillance, Epidemiology and End Results (SEER) database, we identified individuals ≥30 years of age with appendiceal or cecal adenocarcinoma from 1975 to 2016. Demographic, clinical and county-level socioeconomic data were extracted using SEER*Stat software. Survival was compared by Mantel-Haenszel log-rank test, and survival curves were generated using the Kaplan-Meier method. Relative HRs for death in the 5-year period following diagnosis were calculated using multivariable Cox regression analysis, adjusted for all other covariates. The significance level was set at p<0.05 for two-tailed tests. Data were analysed using SAS V.9.4 and R software. RESULTS: We identified 6491 patients with appendiceal adenocarcinoma and 99 387 patients with cecal adenocarcinoma. Multivariable Cox regression analysis demonstrated significantly higher cancer-specific and overall survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. Male sex, older age, earlier year of diagnosis, black race, single marital status, non-Hispanic ethnicity, and non-mucinous histology were associated with increased mortality rates. In addition, counties with lower percentage of individuals below the poverty line and higher colorectal cancer screening rates had better survival. CONCLUSION: This is the first study to show greater survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. We also highlighted novel associations of county-level socioeconomic factors with increased mortality in appendiceal adenocarcinoma. Future efforts to develop targeted molecular therapies and reduce socioeconomic barriers to diagnosis and treatment are warranted to improve survival.

Do looks matter in supply chain contracting? An experimental study.

We present results of an experiment designed to reveal the "face effect" on pricing behavior in a supply chain game. In particular, we study the variation in wholesale prices driven by subjective judgments of three facial traits-attractiveness, trustworthiness, and dominance-of a retailer's face and own appearance. Our experimental data suggest that the distributions of decisions in settings whether individuals see, or not see, retailers' faces are not equivalent. Furthermore, we find the complex dependencies between decision behaviors and facial traits. Subjective evaluations of facial traits, both self-reported and others, have a significant effect on the selected decisions.

Mapping and understanding of correlated electroencephalogram (EEG) responses to the newsvendor problem.

Decision-making is one of the most critical activities of human beings. To better understand the underlying neurocognitive mechanism while making decisions under an economic context, we designed a decision-making paradigm based on the newsvendor problem (NP) with two scenarios: low-profit margins as the more challenging scenario and high-profit margins as the less difficult one. The EEG signals were acquired from healthy humans while subjects were performing the task. We adopted the Correlated Component Analysis (CorrCA) method to identify linear combinations of EEG channels that maximize the correlation across subjects ([Formula: see text]) or trials ([Formula: see text]). The inter-subject or inter-trial correlation values (ISC or ITC) of the first three components were estimated to investigate the modulation of the task difficulty on subjects' EEG signals and respective correlations. We also calculated the alpha- and beta-band power of the projection components obtained by the CorrCA to assess the brain responses across multiple task periods. Finally, the CorrCA forward models, which represent the scalp projections of the brain activities by the maximally correlated components, were further translated into source distributions of underlying cortical activity using the exact Low Resolution Electromagnetic Tomography Algorithm (eLORETA). Our results revealed strong and significant correlations in EEG signals among multiple subjects and trials during the more difficult decision-making task than the easier one. We also observed that the NP decision-making and feedback tasks desynchronized the normalized alpha and beta powers of the CorrCA components, reflecting the engagement state of subjects. Source localization results furthermore suggested several sources of neural activities during the NP decision-making process, including the dorsolateral prefrontal cortex, anterior PFC, orbitofrontal cortex, posterior cingulate cortex, and somatosensory association cortex.

A Computational Procedure for Atomistic Modelling of Polyphosphazenes towards Better Capturing Molecular-Level Structuring and Thermo-Mechanical Properties.

Poly(phosphazenes)(PZ) are versatile polymers due to their tunable properties that can be tailored for specific applications. Despite extensive experimental research, not all properties are tested, and the list of PZs studied via molecular simulations is limited. Further, a general procedure to generate and test PZ systems is lacking. We present an in situ polymerization procedure developed to make, test, and tune the thermo-mechanical properties of four PZs-poly(dichlorophosphazene)(PZ-DC), poly[bis(2,2,2-trifluoroethoxy)]phosphazene (PZ-TFE), poly(2,2,2-trifluoroethoxy-5,6-diazidohexanoxy) phosphazene (PZ-Azido), and poly(2,2,2-trifluoroethoxy-5,6-dinitratohexanoxy)phosphazene (PZ-Nitrato) via molecular dynamics simulations. The predicted thermo-mechanical properties (i.e., density and glass transition temperature) agreed with experimental values when a direct comparison of PZ systems was possible. This demonstrates the reproducibility and reliability of our procedure which will help understand the behaviour of PZs at the molecular scale.

A Shock-Like Pain and Inability to Ambulate: Thoracic Spinal Cord Compression from Hepatocellular Carcinoma.

Hepatocellular carcinoma commonly metastasizes to organs, but there are few reports of vertebral metastases causing cord compression. Here, we present a case of thoracic cord compression in a patient with advanced hepatocellular carcinoma. Providers' and patient's awareness of this risk is important, as this is an oncological emergency.

Alterations of Cerebral Hemodynamics and Network Properties Induced by Newsvendor Problem in the Human Prefrontal Cortex.

While many publications have reported brain hemodynamic responses to decision-making under various conditions of risk, no inventory management scenarios, such as the newsvendor problem (NP), have been investigated in conjunction with neuroimaging. In this study, we hypothesized (I) that NP stimulates the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) joined with frontal polar area (FPA) significantly in the human brain, and (II) that local brain network properties are increased when a person transits from rest to the NP decision-making phase. A 77-channel functional near infrared spectroscopy (fNIRS) system with wide field-of-view (FOV) was employed to measure frontal cerebral hemodynamics in response to NP in 27 healthy human subjects. NP-induced changes in oxy-hemoglobin concentration, Δ[HbO], were investigated using a general linear model (GLM) and graph theory analysis (GTA). Significant activation induced by NP was shown in both DLPFC and OFC+FPA across all subjects. Specifically, higher risk NP with low-profit margins (LM) activated left-DLPFC but deactivated right-DLPFC in 14 subjects, while lower risk NP with high-profit margins (HM) stimulated both DLPFC and OFC+FPA in 13 subjects. The local efficiency, clustering coefficient, and path length of the network metrics were significantly enhanced under NP decision making. In summary, multi-channel fNIRS enabled us to identify DLPFC and OFC+FPA as key cortical regions of brain activations when subjects were making inventory-management risk decisions. We demonstrated that challenging NP resulted in the deactivation within right-DLPFC due to higher levels of stress. Also, local brain network properties were increased when a person transitioned from the rest phase to the NP decision-making phase.

Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability.

Multiple cardiac pathologies are accompanied by loss of tissue excitability, which leads to a range of heart rhythm disorders (arrhythmias). In addition to electronic device therapy (i.e. implantable pacemakers and cardioverter/defibrillators), biological approaches have recently been explored to restore pacemaking ability and to correct conduction slowing in the heart by delivering excitatory ion channels or ion channel agonists. Using optogenetics as a tool to selectively interrogate only cells transduced to produce an exogenous excitatory ion current, we experimentally and computationally quantify the efficiency of such biological approaches in rescuing cardiac excitability as a function of the mode of application (viral gene delivery or cell delivery) and the geometry of the transduced region (focal or spatially-distributed). We demonstrate that for each configuration (delivery mode and spatial pattern), the optical energy needed to excite can be used to predict therapeutic efficiency of excitability restoration. Taken directly, these results can help guide optogenetic interventions for light-based control of cardiac excitation. More generally, our findings can help optimize gene therapy for restoration of cardiac excitability.

Cardiac Optogenetics: Enhancement by All-trans-Retinal.

All-trans-Retinal (ATR) is a photosensitizer, serving as the chromophore for depolarizing and hyperpolarizing light-sensitive ion channels and pumps (opsins), recently employed as fast optical actuators. In mammalian optogenetic applications (in brain and heart), endogenous ATR availability is not considered a limiting factor, yet it is unclear how ATR modulation may affect the response to optical stimulation. We hypothesized that exogenous ATR may improve light responsiveness of cardiac cells modified by Channelrhodopsin2 (ChR2), hence lowering the optical pacing energy. In virally-transduced (Ad-ChR2(H134R)-eYFP) light-sensitive cardiac syncytium in vitro, ATR supplements ≤2 µM improved cardiomyocyte viability and augmented ChR2 membrane expression several-fold, while >4 µM was toxic. Employing integrated optical actuation (470 nm) and optical mapping, we found that 1-2 µM ATR dramatically reduced optical pacing energy (over 30 times) to several µW/mm(2), lowest values reported to date, but also caused action potential prolongation, minor changes in calcium transients and no change in conduction. Theoretical analysis helped explain ATR-caused reduction of optical excitation threshold in cardiomyocytes. We conclude that cardiomyocytes operate at non-saturating retinal levels, and carefully-dosed exogenous ATR can enhance the performance of ChR2 in cardiac cells and yield energy benefits over orders of magnitude for optogenetic stimulation.